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Biomedical subjects

K Nakahara

Publications and source records attributed to K Nakahara.

At least 19 recordsLinked to original sources
PubMed2006

Clinical outcome and risk factors for recurrence in borderline ovarian tumours.

We investigated the long-term prognosis of borderline ovarian tumours and determined risk factors for recurrence. One hundred and twenty-one borderline ovarian tumours treated between 1994 and 2003 at the participating institutions in the Tohoku Gynecologic Cancer Unit were retrospectively investigated for clinical stage, histopathological subtype, surgical technique, postoperative chemotherapy, the presence or absence of recurrence, and prognosis. The median follow-up period was 57 months (1-126 months). One hundred and nine cases (90.6%) were at clinical stage I. The histopathological subtypes consisted of 91 cases of mucinous tumour (75.2%), 27 cases of serous tumour (22.3%), and three cases of endometrioid tumour. Conservative surgery was used in 53 cases (43.8%), radical surgery in 68 cases (56.2%), a staging laparotomy in 43 cases (35.5%), and postoperative adjuvant therapy in 30 cases (24.8%). Recurrence was found in eight cases, but no tumour-related deaths were reported. Although no significant difference in disease-free survival rate was seen between different clinical stages, the difference in disease-free survival rate between serous and non-serous (mucinous and endometrioid) types was significant (P<0.05). The 10-year disease-free survival rate was 89.1% for the radical surgery group and 57.4% for the conservative surgery group -- this difference was significant (P<0.05). In the conservative surgery group, cystectomy and serous tumour were independent risk factors for recurrence. Although recurrence was observed, the long-term prognosis of borderline ovarian tumour was favourable, without tumour-related deaths. Considering the favourable prognosis, conservative surgery can be chosen as far as the patient has a non-serous tumour and receive adnexectomy. However, in cases of serous type and/or receiving cystectomy special care should be given as relative risk rates of recurrence elevate by 2-4-folds.

Adult↗
PubMed2006

Adenosine A1 receptor antagonist improves intradialytic hypotension.

Intradialytic hypotension is a most frequent complication of hemodialysis and may contribute to cardiovascular events and high mortality. There is a hypothesis that an increase in adenosine generation during hemodialysis may cause vasodilation and a decrease in cardiac output, which results in systemic hypotension. We studied whether this can be blocked by an adenosine A1 receptor antagonist. We investigated the effects of an A1 antagonist, FK352, injection in 30 chronic hemodialysis patients with frequent intradialytic hypotension by a prospective, multicenter, double-blind placebo-controlled study for 4 weeks after 4 weeks of the observation period. Intradialytic hypotension was defined as systolic blood pressure (SBP) less than 110 mmHg, with SBP drop of more than 30 mmHg from the predialysis level. The efficacy of FK352 was primarily assessed by the reduction rate of dialysis hypotension between the FK352 and placebo groups. Incidence of emergency treatments caused by hypotension was evaluated. FK352 (50 mg, intravenous) or an equivalent placebo was injected into the dialysis circuit 1 h after starting dialysis. Blood pressure and heart rate were monitored every 30 min during dialysis. FK352 significantly improved intradialytic hypotension (P=0.046), in that the reduction rates of intradialytic hypotension in the FK352 and placebo groups were -12.8% (Q1 (first quantile), Q3 (third quantile): -27.5, -1.7), and +8.3% (Q1, Q3: -16.6, +16.7), respectively. The frequency of discontinuation of dialysis was significantly reduced by FK352. No apparent side effects were observed from treatment with FK352. In conclusion, the A1 antagonist FK352 may offer a novel therapeutic option for chronic dialysis patients associated with intradialytic hypotension.

Adenosine↗
PubMed2005

Strange-quark contributions to parity-violating asymmetries in the forward g0 electron-proton scattering experiment.

We have measured parity-violating asymmetries in elastic electron-proton scattering over the range of momentum transfers 0.12 < or =Q2 < or =1.0 GeV2. These asymmetries, arising from interference of the electromagnetic and neutral weak interactions, are sensitive to strange-quark contributions to the currents of the proton. The measurements were made at Jefferson Laboratory using a toroidal spectrometer to detect the recoiling protons from a liquid hydrogen target. The results indicate nonzero, Q2 dependent, strange-quark contributions and provide new information beyond that obtained in previous experiments.

Journal Article↗
PubMed2005

Stem cell division is regulated by the microRNA pathway.

One of the key characteristics of stem cells is their capacity to divide for long periods of time in an environment where most of the cells are quiescent. Therefore, a critical question in stem cell biology is how stem cells escape cell division stop signals. Here, we report the necessity of the microRNA (miRNA) pathway for proper control of germline stem cell (GSC) division in Drosophila melanogaster. Analysis of GSCs mutant for dicer-1 (dcr-1), the double-stranded RNaseIII essential for miRNA biogenesis, revealed a marked reduction in the rate of germline cyst production. These dcr-1 mutant GSCs exhibit normal identity but are defective in cell cycle control. On the basis of cell cycle markers and genetic interactions, we conclude that dcr-1 mutant GSCs are delayed in the G1 to S transition, which is dependent on the cyclin-dependent kinase inhibitor Dacapo, suggesting that miRNAs are required for stem cells to bypass the normal G1/S checkpoint. Hence, the miRNA pathway might be part of a mechanism that makes stem cells insensitive to environmental signals that normally stop the cell cycle at the G1/S transition.

Animals↗
PubMed2004

Juvenile form of Alexander disease with GFAP mutation and mitochondrial abnormality.

The authors report a 29-year-old woman with marked atrophy of the cerebellum, medulla oblongata, and spinal cord, dementia, diffuse white matter abnormality on MRI, ragged-red fibers, and R88C mutation in the human glial fibrillary acidic protein (GFAP). Mitochondria DNA (mtDNA) analysis showed a rare polymorphism at A8291G. This mtDNA polymorphism, which has been associated with limb-girdle type mitochondrial myopathy, may modify the clinical symptoms of this juvenile form of Alexander disease with GFAP mutation.

Adult↗
PubMed2003

Antibacterial activity of extracts from some edible plants commonly consumed in Asia.

Extracts of edible plants (26 species) from China, Japan, Thailand and Yemen were screened for their antibacterial activity against Bacillus cereus, Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Salmonella infantis. Buffered methanol (80% methanol and 20% PBS) and acetone extracted inhibitory substances against tested bacteria from 16 plants, as revealed by the disc assay. The minimum inhibitory concentrations (MICs) of extracts determined by the agar dilution method ranged from 165 to 2640 mg l(-1). The most sensitive microorganism to extracts from Azadirachta indica, Cinnamomum cassia, Rumex nervosus, Ruta graveolens, Thymus serpyllum and Zingiber officinale was B. cereus, with MIC of 165 to 660 mg l(-1). E. coli and S. infantis were only inhibited by Cinnamomum cassia extracts at the highest MIC (2640 mg l(-1)). L. monocytogenes (Tottori) was more resistant than the ATCC 7644 strain to extracts from Ruta chalepensis, Artemisia absinthium and Cissus spp. EDTA (0.85 mM) reduced the MICs of Cinnamomum cassia and Cissus rotundifolia by at least 50% when tested against E. coli, S. infantis, S. aureus and L. monocytogenes.

Asia↗
PubMed2003

Estrogen and raloxifene induce apoptosis by activating p38 mitogen-activated protein kinase cascade in synthetic vascular smooth muscle cells.

Proliferation of vascular smooth muscle cells (VSMC) plays a major role as an initiating event of atherosclerosis. Although estrogen directly inhibits the proliferation of VSMC, the mechanism has not been firmly established. In addition, the effect of raloxifene on VSMC remains unknown. 17Beta-estradiol (E(2)) and raloxifene significantly inhibited the growth of VSMC under growth-stimulated conditions. Since mitogen-activated protein (MAP) kinases have been implicated in VSMC proliferation, the role of MAP kinases in both the E(2)- and raloxifene-induced growth inhibition of VSMC was studied. Both E(2) and raloxifene caused rapid, transient phosphorylation and activation of p38 that was not affected by actinomycin D and was blocked by ICI 182,780. In contrast with p38 phosphorylation, extracellular signal-regulated protein kinase (ERK) phosphorylation was significantly inhibited and c-Jun N-terminal kinase (JNK) phosphorylation was not changed by E(2). Because VSMC expressed both estrogen receptor (ER) alpha and ERbeta, it is not known which of them mediates the E(2)-induced phosphorylation of p38. Although E(2) did not affect the p38 phosphorylation in A10 smooth muscle cells, which express ERbeta but not ERalpha, transfection of ERalpha expression vector into A10 cells rendered them susceptible to induction of p38 phosphorylation by E(2). We then examined whether E(2) and raloxifene induce apoptosis through a p38 cascade. Both E(2) and raloxifene induced apoptosis under growth-stimulated conditions. The p38 inhibitor SB 203580 completely blocked the E(2)-induced apoptosis. Our findings suggest that both E(2)- and raloxifene-induced inhibition of VSMC growth is due to induction of apoptosis through a p38 cascade whose activation is mediated by ERalpha via a nongenomic mechanism.

Animals↗
PubMed2002

Quantification of minimal residual disease in patients with e1a2 BCR-ABL-positive acute lymphoblastic leukemia using a real-time RT-PCR assay.

Using a real-time RT-PCR method, we analyzed the expression of e1a2 BCR-ABL mRNA in bone marrow samples from 13 patients with e1a2 BCR-ABL-positive acute lymphoblastic leukemia (ALL) at different time points during chemotherapy and after bone marrow transplantation (BMT). The detection limit of the method, assessed using serial dilutions of ALL/MIK cells, was found to be 1:10(5), similar to what is observed for the conventional RT-nested PCR method. The e1a2 BCR-ABL values were normalized with respect to those of the housekeeping gene GAPDH. The decrease in the e1a2 BCR-ABL/GAPDH ratio after remission induction chemotherapy reflects well the response to chemotherapy and consequently correlates with the prognosis. Although molecular remission was achieved by chemotherapy alone, some patients relapsed, and the e1a2 BCR-ABL/GAPDH ratios in these cases progressively increased to the levels seen prior to hematological relapse. Long-term hematological complete remission (more than 30 months) could be achieved in cases in which a more than 4.0 log decrease in the e1a2 BCR-ABL/GAPDH ratio was obtained by chemotherapy alone, and BMT was then performed. In conclusion, real-time RT-PCR allows for an evaluation of the kinetics of e1a2 BCR-ABL/GAPDH expression during the various phases of chemotherapy or after BMT and may be effective for the indication and control of disease relapse in Ph-positive ALL patients.

Adult↗
PubMed2002

Treatment of soft tissue injuries to the dorsum of the metacarpophalangeal joint (Boxer's knuckle).

We retrospectively reviewed the surgical treatment for 16 cases of traumatic soft tissue injury to the metacarpophalangeal joint (Boxer's knuckle). A history of trauma was present in all cases and there was an associated extensor tendon dislocation in seven cases. Eight cases were initially treated conservatively, but their symptoms persisted. Intraoperative findings included rupture of the extensor hood or joint capsule in all cases. Surgical closure of the rupture of the joint capsule resulted in a successful outcome in all cases. We consider that conservative treatment of this injury may not be effective when the joint capsule of the metacarpophalangeal joint is ruptured. We recommend arthrography of the metacarpophalangeal joint to assist in the decision as to whether to proceed with surgical or conservative treatment.

Adolescent↗
PubMed2002

Ghrelin in neonatal rats: distribution in stomach and its possible role.

Ghrelin, a 28 amino acid peptide, has recently been isolated from the rat stomach as an endogenous ligand for the GH secretagogue receptor. The fact that administration of ghrelin, centrally or peripherally, stimulates both food intake and GH secretion suggests that stomach ghrelin has an important role in the growth of rats. We used immunohistochemistry and radioimmunoassay to determine the age at which ghrelin-immunostained cells begin to appear in the rat stomach. Ghrelin-immunoreactive cells were found to be expressed in the fetal stomach from pregnancy day 18. The number of ghrelin-immunoreactive cells in the fetal stomach increased as the stomach grew. The amount of ghrelin in the glandular part of the rat stomach also increased, in an age-dependent manner, from the neonatal stage to adult. Eight hours of milk restriction significantly decreased the ghrelin concentration in the stomachs of 1-week-old rats, and increased the ghrelin concentration in their plasma. Administration of ghrelin to 1- and 3-week-old rats increased plasma GH concentrations. The daily subcutaneous administration of ghrelin to pregnant rats from day 15 to day 21 of pregnancy caused an increase in body weight of newborn rats. In addition, daily subcutaneous administration of ghrelin to neonatal rats from birth advanced the day of vaginal opening from day 30.7+/-0.94 to day 27.9+/-0.05. These results suggest that ghrelin may be involved in neonatal development.

Analysis of Variance↗
PubMed2002

Role for central ghrelin in food intake and secretion profile of stomach ghrelin in rats.

Ghrelin, a 28-amino-acid peptide, has recently been isolated from the rat stomach as an endogenous ligand for the GH secretagogue receptor. We have reported previously that central or peripheral administration of ghrelin stimulates food intake, and the secretion of GH and gastric acid in rats. In the present study, we investigated how much endogenous centrally released ghrelin is involved in the control of food intake and body weight gain. We also examined the profile of ghrelin secretion from the stomach by RIA using two kinds of anti-ghrelin antiserum, one raised against the N-terminal ([Cys(12)]-ghrelin[1-11]) region and one raised against the C-terminal ([Cys(0)]-ghrelin [13-28]) region of the peptide. The former antibody recognizes specifically ghrelin with n- octanoylated Ser 3 (acyl ghrelin), and does not recognize des-acyl ghrelin. The latter also recognizes des-acyl ghrelin (i.e. total ghrelin). Intracerebroventricular treatment with the anti-ghrelin antiserum against the N-terminal region twice a day for 5 days decreased significantly both daily food intake and body weight. Des-acyl ghrelin levels were significantly higher in the gastric vein than in the trunk. Either fasting for 12 h, administration of gastrin or cholecystokinin resulted in increase of both acyl and des-acyl ghrelin levels. The ghrelin levels exhibited a diurnal pattern, with the bimodal peaks occurring before dark and light periods. These two peaks were consistent with maximum and minimum volumes of gastric content respectively. These results suggest that (1) endogenous centrally released ghrelin participates in the regulation of food intake and body weight, (2) acyl ghrelin is secreted from the stomach, (3) intestinal hormones stimulate ghrelin release from the stomach, and (4) regulation of the diurnal rhythm of ghrelin is complex, since ghrelin secretion is augmented under conditions of both gastric emptying and filling.

Animals↗
PubMed2002

[Induction chemoradiotherapy in small adenocarcinoma of the lung with bulky mediatinal lymph node metastasis].

A 56-year-old man, who visited our hospital due to chest pain, was pointed out a large tumor, 60 mm in diameter, on the left superior mediastinum on the chest computed tomography (CT) scan. He was diagnosed as having mediastinal lymph nodes metastasis of adenocarcinoma through video-assisted thoracoscopic surgery (VATS) biopsy. He received induction chemoradiotherapy: cisplatin and paclitaxel were administered once per week for 2 weeks, and radiotherapy was simultaneously performed. No serious adverse reactions were noted. The ipsilateral mediastinal lymph nodes dissection was performed. Intraoperative frozen section analysis showed a small nodule in the left upper lobe, 5 mm in diameter, was adenocarcinoma. He was finally diagnosed as having mediastinal lymph nodes metastasis from the small adenocarcinoma of the lung, and left upper lobectomy was performed. Histopathological examination of the mediastinal lymph nodes showed no evidence of viable maligmant cell. Induction chemoradiotherapy with cisplatin and paclitaxel might be effective treatment for locally advanced non-small cell lung cancer.

Adenocarcinoma↗
PubMed2001

Identification of quercetin 3-O-beta-D-glucuronide as an antioxidative metabolite in rat plasma after oral administration of quercetin.

The potential beneficial effect of dietary quercetin (3,3',4',5,7-pentahydroxyflavone) has attracted much attention in relation to the prevention of cardiovascular disease. It is generally recognized that dietary quercetin is subject to metabolic conversion resulting in conjugated forms during absorption and circulation. However, no quercetin conjugates have yet been identified from biological fluids or tissues. In the present study, we isolated and characterized two quercetin conjugates from the plasma of quercetin-administered rats. The blood plasma was collected from 26 rats 30 min after oral administration of quercetin (250 mg/kg body weight), concentrated, dissolved in 2% acetic acid aqueous solution (pH 2.65), and extracted with ethyl acetate. Two compounds (P2, P3) were obtained from the extract by repeated reversed-phase HPLC. On the other hand, two quercetin glucuronides were synthesized chemically and identified as quercetin 3-O-beta-D-glucuronide (Q3GA) and quercetin 4'-O-beta-D-glucuronide (Q4'GA), as determined from FABMS, 1H- and 13C-NMR, and HMBC data. The retention times of P2 and P3 in the HPLC chromatogram corresponded to those of Q3GA and Q4'GA, respectively. FABMS data demonstrated that P2 and P3 are quercetin monoglucuronides. 1H-NMR data for P2 were completely in agreement with those for Q3GA. P2 was therefore identified as Q3GA. This is, to our knowledge, the first evidence that Q3GA accumulates in vivo after oral administration of quercetin. Q3GA is likely to act as an effective antioxidant in blood plasma low-density lipoprotein, because this conjugated metabolite was found to possess a substantial antioxidant effect on copper ion-induced oxidation of human plasma low-density lipoprotein as well as 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activity.

Administration, Oral↗
PubMed2001

Effect of melatonin on circadian rhythm, locomotor activity and body temperature in the intact house sparrow, Japanese quail and owl.

We compared the effect of melatonin on circadian rhythm, body temperature, and locomotion in the intact house sparrow, Japanese quail and owl. Daily treatment with melatonin at a fixed time did not entrain the free-running rhythm of locomotor activity in the house sparrow and the disrupted rhythm in Japanese quail under constant dim light. However, melatonin clearly inhibited movement for several hours after treatment. The duration of resting after injection of melatonin was dose-dependent. Body temperature was significantly decreased after melatonin treatment, the effect being more potent during the active phase than in the resting phase. Although this effect of melatonin on body temperature was also dose-dependent, the magnitude of the decrease in body temperature after injection of melatonin was greater in the house sparrow than in the Japanese quail. On the other hand, melatonin induced a further large decrease of body temperature in a nocturnal bird, the owl, whose pineal gland is degenerate. The decrease of body temperature was larger in the active phase than in the resting phase, and melatonin did not prevent movement in spite of the decrease in body temperature. These results suggest that the effects of melatonin on circadian rhythm, locomotor activity and body temperature differ among avian species, and that these mechanisms may not be linked to each other.

Animals↗
PubMed2001

Relationship between response of gamma-glutamyl transpeptidase to alcohol drinking and risk factors for coronary heart disease.

Alcohol drinking has been reported to influence the risk factors for coronary heart disease (CHD), such as the serum levels of triglycerides, HDL-cholesterol and uric acid, and the level of blood pressure. To examine whether there was individual variability in the response of these parameters to alcohol drinking, a cross-sectional study was conducted in 3130 men with a body-mass index (BMI) below 24. The subjects were divided into two groups; a normal gamma-glutamyl transpeptidase (rGTP) (<40 IU/l) group and a high rGTP (> or =40 IU/l) group, and the values were compared after adjusted for age, BMI, exercise and smoking. The level of triglycerides increased according to the amount of drinking in the high rGTP group, whereas no association was observed in the normal rGTP group. The level of HDL-cholesterol increased with drinking in the normal and high rGTP groups, and no difference was observed in the levels of HDL-cholesterol between the two groups. The levels of uric acid and blood pressure also increased with drinking in both groups, but the increase was bigger in the high rGTP group than in the normal rGTP group. The results indicated that there was large individual variability in the responses of the risk factors for coronary heart disease to drinking. Subjects whose rGTP responds less to drinking may have less disadvantageous effects of drinking.

Adult↗
PubMed2001

Structural analysis of a novel antimutagenic compound, 4-Hydroxypanduratin A, and the antimutagenic activity of flavonoids in a Thai spice, fingerroot (Boesenbergia pandurata Schult.) against mutagenic heterocyclic amines.

Six compounds were isolated from fresh rhizomes of fingerroot (Boesenbergia pandurata Schult.) as strong antimutagens toward 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) in Salmonella typhimurium TA98. These compounds were 2',4',6'-trihydroxychalcone (pinocembrin chalcone; 1), 2',4'-dihydroxy-6'-methoxychalcone (cardamonin; 2), 5,7-dihydroxyflavanone (pinocembrin; 3), 5-hydroxy-7-methoxyflavanone (pinostrobin; 4), (2,4,6-trihydroxyphenyl)-[3'-methyl-2'-(3' '-methylbut-2' '-enyl)-6'-phenylcyclohex-3'-enyl]methanone (5), and (2,6-dihydroxy-4-methoxyphenyl)-[3'-methyl-2'-(3' '-methylbut-2' '-enyl)-6'-phenylcyclohex-3'-enyl]methanone (panduratin A; 6). Compound 5 was a novel compound (tentatively termed 4-hydroxypanduratin A), and 1 was not previously reported in this plant, whereas 2-4 and 6 were known compounds. The antimutagenic IC(50) values of compounds 1-6 were 5.2 +/- 0.4, 5.9 +/- 0.7, 6.9 +/- 0.8, 5.3 +/- 1.0, 12.7 +/- 0.7, and 12.1 +/- 0.8 microM in the preincubation mixture, respectively. They also similarly inhibited the mutagenicity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). All of them strongly inhibited the N-hydroxylation of Trp-P-2. Thus, the antimutagenic effect of compounds 1-6 was mainly due to the inhibition of the first step of enzymatic activation of heterocyclic amines.

Amines↗